Pre-IDE Submission: Clinical Protocol 
Neuroblastoma Bone Marrow Purging System 
BAXTER HEALTHCARE CORPORATION, HYLAND DIVISION 
The most advanced form of the disease, clinical Stage 4, is metastatic Hiwaw involving 
one or more organs, including, but not limited to the bone marrow (Berthold, 1990). 
This is essentially identical to Stage D in the Pediatric Oncology Group classification 
(Brodeur et al, 1988), (see Appendix A). 
6. 1 . 1 .2 Incidence and Demographics 
The incidence of new cases of neuroblastoma in 1990 was estimated at 500 cases 
worldwide, with the majority of cases diagnosed in the USA (200) and in Europe (200) 
(Graham-Pole, 1990). In a series of 81 patients transplanted by the Pediatric Oncology 
Group (POG) the following demographic profile was reported: me dian age at diagnosis 
- 4 years (range 0.5-14); race - 14% black, 86% non-black; sex - 40% female, 60% 
male (Graham-Pole et al, 1991). 
In a study of 197 patients, at diagnosis 65% were found to be in Stage D. 
Neuroblastoma cells were detected in 66.5 % of all patients, with 86% of Stage D patients 
displaying marrow involvement, with a median of 20,000 tumor cells per 100,000 
marrow cells (Moss et al, 1991). 
6. 1.1.3 Treatment 
Chemotherapy combined with surgery has been the conventional treatment for Stage D 
neuroblastoma. Disease-free-survival using this approach has been 10-20% at 5 years 
(Evans et al, 1987; Green et al, 1986). This has lead to the development and testing of 
protocols to evaluate intensive chemotherapy and total body irradiation with autologous 
bone marrow rescue, as an alternative to conventional therapy. Phase 3 studies have 
indicated that two-year disease-free survival approximates 45 % in Stage D patients, using 
this approach (Graham-Pole et al, 1991). New protocols for the two major study groups 
(POG and the Children’s Cancer Study Group [CCSG]) are being evaluated to modify 
the induction and consolidation chemotherapy in order to further improve outcome. 
Recombinant DNA Research, Volume 16 
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